DNA's performance as an archival medium is spectacular. In its capacity to preserve a message it far outdoes tablets of stone. Cows and pea plants (and, indeed, all the rest of us) have an almost identical gene called the histone H4 gene. The DNA text is 306 characters long. We can't say that it occupies the same addresses in all species, because we can't meaningfully compare address labels across species. But what we can say is that there is a length of 306 characters in cows, which is virtually identical to a length of 306 characters in peas. Cows and peas differ from each other in only two characters out of these 306. We don't know exactly how long ago the common ancestor of cows and peas lived, but fossil evidence suggests that it was somewhere between 1,000 and 2,000 million years ago. Call it 1.5 billion years ago. Over this unimaginably (for humans) long time, each of the two lineages that branched from that remote ancestor has preserved 305 out of the 306 characters (on average: it could be that one lineage has preserved all 306 of them and the other has preserved 304). Letters carved on gravestones become unreadable in mere hundreds of years.
In a way the conservation of the histone-H4 DNA document is even more impressive because, unlike tablets of stone, it is not the same physical structure that lasts and preserves the text. It is repeatedly being copied and recopied as the generations go by, like the Hebrew scriptures which were ritually copied by scribes every 80 years to forestall their wearing-out. It is hard to estimate exactly how many times the histone H4 document has been recopied in the lineage leading to cows from the common ancestor with peas, but it is probably as many as 20 billion times. It is also hard to find a yardstick with which to compare the preservation of more than 99 per cent of information in 20 billion successive copyings. We can try using a version of the game of grandmothers' whispers. Imagine 20 billion typists sitting in a row. The line of typists would reach right round the Earth 500 times. The first typist writes a page of a document and hands it to his neighbour. He copies it and hands his copy to the next one. He copies it again and hands it on to the next, and so on. Eventually, the message reaches the end of the line, and we read it (or rather our 12,000th great grandchildren do, assuming that all the typists have a speed typical of a good secretary!. How faithful a rendering of the original message would it be?
To answer this we have to make some assumption about the accuracy of the typists. Let's twist the question round the other way. How good would each typist have to be, in order to match the DNA's performance' The answer is almost too ludicrous to express. For what it is worth, every typist would have to have an error rate of about one in a trillion; that is, he would have to be accurate enough to make only a single error in typing the Bible 250,000 times at a stretch. A good secretary in real life has an error rate of about one per page. This is about half a billion times the error rate of the histone H4 gene. A line of real-life secretaries would degrade a text to 99 per cent of its original letters by the 20th member of the line of 20 billion. By the 10,000th member of the line, less than 1 per cent of the original text would survive. This point of near total degradation would be reached before 99.9995 per cent of the typists had even seen it.
This whole comparison has been a bit of a cheat, but in an interesting and revealing respect. I gave the impression that what we are measuring is copying errors. But the histone H4 document hasn't just been copied, it has been subjected to natural selection. Histone is vitally important for survival. It is used in the structural engineering of chromosomes. Maybe lots more mistakes in copying the histone H4 gene occurred, but the mutant organisms did not survive, or at least did not reproduce. To make the comparison fair, we should have to assume that built into each typist's chair is a gun, wired up so that if he makes a mistake he is summarily shot, his place being taken by a reserve typist (squeamish readers may prefer to imagine a spring-loaded ejector seat gently catapulting miscreant typists out of the line, but the gun gives a more realistic picture of natural selection).
So, this method of measuring the conservatism of DNA, by looking at the number of changes that have actually occurred during geological time, compounds genuine copying fidelity with the filtering effects of natural selection. We see only the descendants of successful DNA changes. The ones that led to death are obviously not with us. Can we measure the actual copying fidelity on the ground, before natural selection gets to work on each new generation of genes? Yes, this is the inverse of what is known as the mutation rate, and it can be measured. The probability of any particular letter being miscopied on any one copying occasion turns out to be a little more than one in a billion. The difference between this, the mutation rate, and the lower rate at which change has actually been incorporated in the histone gene during evolution, is a measure of the effectiveness of natural selection in preserving this ancient document.
The histone gene's conservatism over the aeons is exceptional by genetic standards. Other genes change at a higher rate, presumably because natural selection is more tolerant of variations in them. For instance, genes coding the proteins known as fibrinopeptides change in evolution at a rate that closely approximates the basic mutation rate. This probably means that mistakes in the details of these proteins (they are produced during the clotting of blood) don't matter much for the organism. Haemoglobin genes have a rate of changing that is intermediate between histones and fibrinopeptides. Presumably natural selection's tolerance of their errors is intermediate. Haemoglobin is doing an important job in the blood, and its details really matter; but several alternative variants of it seem capable of doing the job equally well.
Here we have something that seems a little paradoxical, until we think about it further. The slowest-evolving molecules, like histones, turn out to be the ones that have been most subject to natural selection. Fibrinopeptides are the fastest-evolving molecules because natural selection almost completely ignores them. They are free to evolve at the mutation rate. The reason this seems paradoxical is that we place so much emphasis on natural selection as the driving force of evolution. If there is no natural selection, therefore, we might expect that there would be no evolution. Conversely, strong 'selection pressure', we could be forgiven for thinking, might be expected to lead to rapid evolution. Instead, what we find is that natural selection exerts a braking effect on evolution. The baseline rate of evolution, in the absence of natural selection, is the maximum possible rate. That is synonymous with the mutation rate.
This isn't really paradoxical. When we think about it carefully, we see that it couldn't be otherwise. Evolution by natural selection could not be faster than the mutation rate, for mutation is, ultimately, the only way in which new variation enters the species. All that natural selection can do is accept certain new variations, and reject others. The mutation rate is bound to place an upper limit on the rate at which evolution can proceed. As a matter of fact, most of natural selection is concerned with preventing evolutionary change rather than with driving it. This doesn't mean, I hasten to insist, that natural selection is a purely destructive process. It can construct too, in ways that Chapter 7 will explain.
Even the mutation rate is pretty slow. This is another way of saying that, even without natural selection, the performance of the DNA code in accurately preserving its archive is very impressive. A conservative estimate is that, in the absence of natural selection, DNA replicates so accurately that it takes five million replication generations to miscopy 1 per cent of the characters. Our hypothetical typists are still hopelessly outclassed by DNA, even if there is no natural selection. To match DNA with no natural selection, the typists would each have to be able to type the whole of the New Testament with only one error. That is, they would each have to be about 450 times more accurate than a typical real-life secretary. This is obviously much less than the comparable figure of half a billion, which is the factor by which the histone H4 gene after natural selection is more accurate than a typical secretary; but it is still a very impressive figure.
But I have been unfair to the typists. I assumed, in effect, that they are not capable of noticing their mistakes and correcting them. I have assumed a complete absence of proofreading. In reality, of course, they do proofread. My line of billions of typists wouldn't, therefore, cause the original message to degenerate in quite the simple way that I portrayed. The DNA-copying mechanism does the same kind of error-correction automatically. If it didn't, it wouldn't achieve anything like the stupendous accuracy that I have described. The DNA-copying procedure incorporates various 'proofreading' drills. This is all the more necessary because the letters of the DNA code are by no means static, like hieroglyphs carved in granite. On the contrary, the molecules involved are so small - remember all those New Testaments fitting on a pin's head- that they are under constant assault from the ordinary jostling of molecules that goes on due to heat. There is a constant flux, a turnover of letters in the message. About 5,000 DNA letters degenerate per day in every human cell, and are immediately replaced by repair mechanisms. If the repair mechanisms weren't there and ceaselessly working, the message would steadily dissolve. Proofreading of newly copied text is just a special case of normal repair work. It is mainly proofreading that is responsible for DNA's remarkable accuracy and fidelity of information storage.
